Radionuclides attached to colloid particles have been injected into the joints of patients with persistent joint effusions, the majority of whom respond well. The significant problem to make radiation synovectomy a safer procedure is that of reducing radioactive leakage from the injected joint. We have used a short half-life radionuclide (165Dy-140 minutes) so that only leakage occurring soon after administration will contribute to unwanted exposure and we have contained the activity in ferric hydroxide macroaggregates (FHMA) in the size range of 0.5-5 um, coprecipitated with dysprosium-165. Since the purpose of radiation synovectomy is to protect the joint cartilage, we now propose to evaluate the effect upon articular cartilage of ferric hydroxide and dysprosium-165, separately and combined. The ability of articular cartilage chondrocytes to incorporate radioactive precursors of matrix components will be evaluated after exposure of the cartilage to FHMA and 165Dy. Using the rabbit model of rheumatoid arthritis, antigen induced arthritis, the therapeutic efficacy of radiation synovectomy will be evaluated using histological and histochemical criteria. Correct dosage and methods of decreasing leakage will be determined. In addition, a newly developed biological assay of synovial degradative capacity will be used to evaluate the therapeutic efficacy of radiation synovectomy in rabbits. As the animal studies demonstrate the safety and efficacy of FHMA-165Dy radiation synovectomy, a limited clinical trial in humans is being carried out. Other particle-isotope systems will continue to be evaluated (such as albumin microspheres and liposomes).